Infection with a human-derived enteroinvasive Escherichia coli strain altered intestinal barrier function in guinea pigs / La infección con una cepa enteroinvasiva de Escherichia coli de origen humano alteró la función de la barrera intestinal en cobayos

Background/aims: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. Materials and methods: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. Results: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. Conclusions: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.(AU)

Multiple Mechanistic Models Reveal the Neuroprotective Effects of Diterpene Ginkgolides against Astrocyte-Mediated Demyelination via the PAF-PAFR Pathway.

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.

Infection with a human-derived enteroinvasive Escherichia coli strain altered intestinal barrier function in guinea pigs.

BACKGROUND/AIMS: The aim was to characterize a bacterium causing intestinal mucosal barrier damage and to identify the possible invasion mechanism. MATERIALS AND METHODS: The intestinal permeability and tight junction protein levels were detected in guinea pigs infected with Escherichia coli D-09 via immunofluorescence analysis and western blotting. In order to explain this invasion mechanism at the gene level, whole genome sequencing analysis was performed on this bacterium. RESULTS: The results showed an increased intestinal permeability and upregulated expression of the leaky protein claudin-2 in both the colon and liver of the infected animals. In addition, the draft genome of E. coli D-09 comprised 42 scaffolds (size, > 645 bp) with a total size of 4,679,567 bp. A total of 4379 protein coding genes were identified, which contained 45 antibiotic resistance and 86 virulence-related genes and covered 88.0% of the whole genome. CONCLUSIONS: This study verified that the human-derived enteroinvasive E. coli strain could destroy intestinal barrier function in guinea pigs. Additionally, our data first characterized the genome features of E. coli O124:K72 D-09, which may provide new insights into the possible invasion mechanism.